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Microplastics (MPs) pose a clear threat to aquatic organisms affecting their health. Their impact on liver homeostasis, as well as on the potential onset of nonalcoholic fatty liver disease (NAFLD), is still poorly investigated and remains almost unknown. The aim of this study was to evaluate the outcomes of subchronic exposure to polystyrene MPs (PS-MPs; 1–20 μm; 0, 25, or 250 mg/kg b.w./day) on lipid metabolism, inflammation, and oxidative balance in the liver of gilthead seabreams (Sparus aurata Linnaeus, 1758) exposed for 21 days via contaminated food. PS-MPs induced an up-regulation of mRNA levels of crucial genes associated with lipid synthesis and storage (i.e., PPARy, Srebp1, Fasn) without modifications of genes involved in lipid catabolism (i.e., PPARα, HL, Pla2) or transport and metabolism (Fabp1) in the liver. The increase of CSF1R and pro-inflammatory cytokines gene expression (i.e., TNF-α and IL-1β) was also observed in exposed fish in a dose-dependent manner. These findings were confirmed by hepatic histological evaluations reporting evidence of lipid accumulation, inflammation, and necrosis. Moreover, PS-MPs caused the impairment of the hepatic antioxidant defense system through the alteration of its enzymatic (catalase, superoxide dismutase, and glutathione reductase) and non-enzymatic (glutathione) components, resulting in the increased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as biomarkers of oxidative damage. The alteration of detoxifying enzymes was inferred by the decreased Ethoxyresorufin-O-deethylase (EROD) activity and the increased activity of glutathione-S-transferase (GST) at the highest PS-MP dose. The study suggests that PS-MPs affect the liver health of gilthead seabream. The liver dysfunction and damage caused by exposure to PS-MPs result from a detrimental interplay of inflammation, oxidative damage, and antioxidant and detoxifying enzymatic systems modifications, altering the gut-liver axis homeostasis. This scenario is suggestive of the involvement of MP-induced effects in the onset and progression of hepatic lipid dysfunction in gilthead seabream.

The role of the cortex in shaping automatic whole-body motor behaviors such as walking and balance is poorly understood. Gait and balance are typically mediated through subcortical circuits, with the cortex becoming engaged as needed on an individual basis by task difficulty and complexity. However, we lack a mechanistic understanding of how increased cortical contribution to whole-body movements shapes motor output. Here we use reactive balance recovery as a paradigm to identify relationships between hierarchical control mechanisms and their engagement across balance tasks of increasing difficulty in young adults. We hypothesize that parallel sensorimotor feedback loops engaging subcortical and cortical circuits contribute to balance-correcting muscle activity, and that the involvement of cortical circuits increases with balance challenge. We decomposed balance-correcting muscle activity based on hypothesized subcortically- and cortically-mediated feedback components driven by similar sensory information, but with different loop delays. The initial balance-correcting muscle activity was engaged at all levels of balance difficulty. Its onset latency was consistent with subcortical sensorimotor loops observed in the lower limb. An even later, presumed, cortically-mediated burst of muscle activity became additionally engaged as balance task difficulty increased, at latencies consistent with longer transcortical sensorimotor loops. We further demonstrate that evoked cortical activity in central midline areas measured using electroencephalography (EEG) can be explained by a similar sensory transformation as muscle activity but at a delay consistent with its role in a transcortical loop driving later cortical contributions to balance-correcting muscle activity. These results demonstrate that a neuromechanical model of muscle activity can be used to infer cortical contributions to muscle activity without recording brain activity. Our model may provide a useful framework for evaluating changes in cortical contributions to balance that are associated with falls in older adults and in neurological disorders such as Parkinson's disease.

Myeloproliferative neoplasms (MPNs) are subdivided into Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is essential for the development and diagnosis of CML; on the other hand, the majority of Ph-negative MPNs are characterized by generally mutually exclusive mutations of Janus kinase 2 (JAK2), calreticulin (CALR), or thrombopoietin receptor/myeloproliferative leukemia (MPL). CALR mutations have been described essentially in JAK2 and MPL wild-type essential thrombocythemia and primary myelofibrosis. Rarely coexisting CALR and MPL mutations have been found in Ph-negative MPNs. BCR::ABL1 translocation and JAK2 mutations were initially considered mutually exclusive genomic events, but a discrete number of cases with the combination of these genetic alterations have been reported. The presence of BCR::ABL1 translocation with a coexisting CALR mutation is even more uncommon. Herein, starting from a routinely diagnosed case of CALR-mutated primary myelofibrosis subsequently acquiring BCR::ABL1 translocation, we performed a comprehensive review of the literature, discussing the clinicopathologic and molecular features, as well as the outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence.

Myeloproliferative neoplasms (MPNs) are classified into Philadelphia (Ph) chromosome–positive chronic myeloid leukemia (CML) and Ph-negative MPNs. BCR::ABL1 translocation is the key genetic event of CML, whereas JAK2/MPL/CALR mutations are molecular aberrations of Ph-negative MPNs. Despite initially considered mutually exclusive genetic aberrations, the co-occurrence of BCR::ABL1 and JAK2 has been reported in a limited number of cases. The two genetic alterations may be identified either at the same time or JAK2 aberration may be detected in patients with a previous CML treated with tyrosine kinase inhibitors or, finally, BCR::ABL1 translocation occurs in patients with a history of JAK2-positive MPN. This combination of genomic alterations is potentially confounding with clinical manifestations often misinterpreted either as disease progression or drug resistance, therefore leading to inappropriate patient’s treatment. Our systematic review aims to improve hematologist and pathologist knowledge on this rare subset of patients. Starting from the presentation of two additional cases from our routine daily practice, we focus mainly on clinical, laboratory, and bone marrow histological findings, which may represent useful clues of BCR::ABL1 and JAK2 co-occurrence. The interaction between JAK2 and BCR::ABL1 clones during the disease course as well as therapy and outcome are presented.

Mantle cell lymphoma is a B-cell malignancy, which, in its classic form, usually involves lymph nodes and extranodal sites, and, among the extranodal sites, the gastrointestinal tract and the Waldeyer’s ring are most prevalent. MCL is rarely reported in the ocular adnexa, a site more frequently affected by extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, which is a form of low-grade malignancy. The diagnosis of MCL presenting in the ocular adnexa requires special attention as its rarity in this location combined with the not uncommon CD5 negativity of the disease when occurring in the ocular adnexa, may lead the pathologist to overlook the diagnosis and misinterpret MCL as marginal zone B cell lymphoma, which has a totally different behavior. Herein, we present a case of primary bilateral conjunctival CD5-negative MCL in a patient having no other sites affected by lymphoma and we discuss possible diagnostic pitfalls.

Long non-coding RNA (lncRNA) are emerging as powerful and versatile regulators of transcriptional programs and distinctive biomarkers of progression of T-cell lymphoma. Their role in the aggressive anaplastic lymphoma kinase-negative (ALK–) subtype of anaplastic large cell lymphoma (ALCL) has been elucidated only in part. Starting from our previously identified ALCL-associated lncRNA signature and performing digital gene expression profiling of a retrospective cohort of ALCL, we defined an 11 lncRNA signature able to discriminate among ALCL subtypes. We selected a not previously characterized lncRNA, MTAAT, with preferential expression in ALK– ALCL, for molecular and functional studies. We demonstrated that lncRNA MTAAT contributes to an aberrant mitochondrial turnover restraining mitophagy and promoting cellular proliferation. Functionally, lncRNA MTAAT acts as a repressor of a set of genes related to mitochondrial quality control via chromatin reorganization. Collectively, our work demonstrates the transcriptional role of lncRNA MTAAT in orchestrating a complex transcriptional program sustaining the progression of ALK– ALCL.

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient’s work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed.

Here we show the SAVEMEDCOASTS-2 web-based geographic information system (webGIS) that supports land planners and decision makers in considering the ongoing impacts of Relative Sea Level Rise (RSLR) when formulating and prioritizing climate-resilient adaptive pathways for the Mediterranean coasts. The webGIS was developed within the framework of the SAVEMEDCOASTS and SAVEMEDCOASTS-2 projects, funded by the European Union, which respond to the need to protect people and assets from natural disasters along the Mediterranean coasts that are vulnerable to the combined effects of Sea Level Rise (SLR) and Vertical Land Movements (VLM). The geospatial data include available or new high-resolution Digital Terrain Models (DTM), bathymetric data, rates of VLM, and multi-temporal coastal flooding scenarios for 2030, 2050, and 2100 with respect to 2021, as a consequence of RSLR. The scenarios are derived from the 5th Assessment Report (AR5) provided by the Intergovernmental Panel on Climate Change (IPCC) and encompass different Representative Concentration Pathways (RCP2.6 and RCP8.5) for climate projections. The webGIS reports RSLR scenarios that incorporate the temporary contribution of both the highest astronomical tides (HAT) and storm surges (SS), which intensify risks to the coastal infrastructure, local community, and environment.

Abstract Background Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed. Methods We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms “primary effusion lymphoma” and “post-transplant”. Results Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted. Conclusions Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.

Mycosis fungoides (MF) is defined as an epidermotropic primary cutaneous T-cell lymphoma composed of small-to-medium-sized T lymphocytes with cerebriform nuclei and with a T-helper phenotype. LeBoit first described an unusual variant of MF with dermal acid mucin deposition. Such a variant was still considered in the list of clinicopathological variants of MF by Cerroni and colleagues. We herein report a case of patch-stage MF with abundant papillary dermal mucin deposition in a clinical setting of an erythematous patch on the lower abdomen and thigh.

Abstract Background Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract is a rare low-grade clonal lymphoid proliferation, included as a provisional entity in the current World Health Organization classification. The disease is generally localized to the gastrointestinal tract, mainly small bowel and colon. Involvement of other organs is infrequently reported. The majority of patients show a protracted clinical course with persistent disease. A prolonged survival, even without treatment, is common. Case presentation A 28-year-old woman had a 2-year history of dyspepsia and lactose intolerance. Autoimmune diseases and celiac disease were excluded. No gross lesions were identified by endoscopy. Multiple gastric biopsies showed a small-sized lymphoid infiltrate, expanding the lamina propria, with a non-destructive appearance. The lymphoid cells were positive for CD3, CD4, CD5, CD7 and negative for CD20, CD8, CD56, CD103, PD1, CD30, ALK1, CD10, BCL6, perforin, TIA-1, Granzyme B and Epstein-Barr virus-encoded RNA. KI-67 index was low (5%). Molecular analysis revealed a clonal T-cell receptor γ rearrangement. Bone marrow was microscopically free of disease, but molecular testing identified the same T-cell receptor γ rearrangement present in the gastric biopsies. After the diagnosis of indolent T-cell lymphoproliferative disorder of the gastrointestinal tract, the patient received steroid therapy, only for 2 months. She is alive, with a stable disease restricted to the stomach, at 12 months from diagnosis. Conclusions Indolent T-cell lymphoproliferative disorder is usually a disease of adulthood (median age: 51 yrs). The small bowel and colon are the sites most commonly involved. Our case occurred in a young woman and affected the stomach, sparing small intestine and colon. Clonality testing identified involvement of bone marrow, a site infrequently affected in this disease. Our aim is focusing on the main diagnostic issues. If appropriate immunostainings and molecular analysis are not performed, the subtle infiltrate may be easily overlooked. The risk of misdiagnosis as more aggressive lymphomas, causing patient overtreatment, needs also to be considered.

A 57-year-old man affected by high-risk progressive chronic lymphocytic leukemia (CLL), primary resistant to first-line chemoimmunotherapy, developed a type A lymphomatoid papulosis (LyP) during a second progression of CLL. The two blood tumor entities were clonally unrelated. LyP presented with a diffuse (>90% body surface area) cutaneous rash and was characterized by intensely pruriginous dusky nodules (n = 10) and red flat-topped papules (n = 60). No response to topical corticosteroids and psoralen plus ultraviolet A (PUVA) phototherapy was observed. In order to effectively treat progressive TP53-mutated CLL, the potent BCL2 inhibitor, venetoclax, was initiated with no treatment-related complications. While CLL only achieved a partial response, a complete remission of LyP-associated cutaneous rash and of the intractable pruritus was obtained within 2 months from venetoclax initiation. BCL2 immunostaining of the original cutaneous specimen showed a strong over-expression of the anti-apoptotic protein, restricted to CD30+ lymphoid cells and reactive microenvironment. At 12 months follow-up, the patient is still in complete remission of LyP. Our findings underline the probable pathogenic role of BCL2 in LyP and the potential therapeutic efficacy of venetoclax for the treatment of this primary cutaneous CD30+ lymphoproliferative disorder, especially in the setting of severe and refractory disease.

Abstract Background Eosinophilic lung diseases represent a heterogeneous group of disorders with prominent infiltrate of eosinophils in lung interstitium and alveolar spaces. Peripheral blood eosinophilia is often present. Infections, drugs, allergens, toxic agents have to be evaluated as possible causes of eosinophilic lung infiltrates. The category of myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2 represents an uncommon cause of eosinophilic lung infiltrate. Case presentation We report the case of a 70-year old man complaining of dry cough and dyspnea. Ground glass-opacities were seen on imaging studies and peripheral blood eosinophilia was present. A thorough step-wise patient’s evaluation led to identify the clonal nature of eosinophilia and the diagnosis of myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA was made. Conclusions Correlation with clinical history, laboratory tests and imaging studies is essential to achieve the correct diagnosis when facing with eosinophilic lung infiltrates. A prolonged eosinophilia can cause life-threatening organ damage. Identification of PDGFRA rearrangement, as in the present case, is particularly critical given the sensitivity and excellent response to imatinib, which has completely changed the natural history of this neoplasm.

Abstract Background Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is a rare Epstein-Barr virus (EBV) positive lymphoproliferative disorder included in the current World Health Organization (WHO) classification. It arises within fibrinous material in the context of hematomas, pseudocysts, cardiac myxoma or in relation with prosthetic devices. In these clinical settings the diagnosis requires an high index of suspicion, because it does not form a mass itself, being composed of small foci of neoplastic cells. Despite overlapping features with diffuse large B-cell lymphoma associated with chronic inflammation, it deserves a separate classification, being not mass-forming and often following an indolent course. Case presentation A 64-year-old immunocompetent woman required medical care for cerebral hemorrhage. Computed Tomography (CT) angiography identified an aneurysm in the left middle cerebral artery. A FA-DLBCL was incidentally identified within thrombotic material in the context of the arterial aneurysm. After surgical removal, it followed a benign course with no further treatment. Conclusions The current case represents the first report of FA-DLBCL identified in a cerebral artery aneurysm, expanding the clinicopathologic spectrum of this rare entity. A complete literature review is additionally made.

Coasts are highly dynamic and geo-morphologically complex systems that are exposed to several factors such as waves, extreme meteorological events and climate change. It is also well-recognized that coastal zones, characterized by an increasing population growth, are vulnerable to climate change. In addition, coastal erosion, resulting from natural environment changes and human activities, acts worldwide. Consequently, it is necessary to quantify coastal hazards vulnerability and develop tools to monitor coastal risks and support making targeted climate adaptation policies. In this paper, a framework to estimate coastal vulnerability to flooding and erosion has been developed for the Ionian Basilicata coast. It is based on two methods: the integrated vulnerability index (flooding and erosion) and the CeD physical vulnerability index (multi-risk assessment). Our results are in agreement with the recent shoreline evolution: the integrated coastal risk of the Ionian Basilicata coast is generally medium to high, while the “physical erosion vulnerability” is generally high to very high. In addition, the results highlight a spatial variability of the vulnerability, probably due to the morphology of the beach, which requires developing a strategic approach to coastal management and defining mitigation measures, considering relevant risk aspects as the vulnerability and exposure degree.

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Leg rigidity is associated with frequent falls in people with Parkinson’s disease (PD), suggesting a potential role in functional balance and gait impairments. Changes in the neural state due to secondary tasks, e.g., activation maneuvers, can exacerbate (or “activate”) rigidity, possibly increasing the risk of falls. However, the subjective interpretation and coarse classification of the standard clinical rigidity scale has prohibited the systematic, objective assessment of resting and activated leg rigidity. The pendulum test is an objective diagnostic method that we hypothesized would be sensitive enough to characterize resting and activated leg rigidity. We recorded kinematic data and electromyographic signals from rectus femoris and biceps femoris during the pendulum test in 15 individuals with PD, spanning a range of leg rigidity severity. From the recorded data of leg swing kinematics, we measured biomechanical outcomes including first swing excursion, first extension peak, number and duration of the oscillations, resting angle, relaxation index, maximum and minimum angular velocity. We examined associations between biomechanical outcomes and clinical leg rigidity score. We evaluated the effect of increasing rigidity through activation maneuvers on biomechanical outcomes. Finally, we assessed whether either biomechanical outcomes or changes in outcomes with activation were associated with a fall history. Our results suggest that the biomechanical assessment of the pendulum test can objectively quantify parkinsonian leg rigidity. We found that the presence of high rigidity during clinical exam significantly impacted biomechanical outcomes, i.e., first extension peak, number of oscillations, relaxation index, and maximum angular velocity. No differences in the effect of activation maneuvers between groups with clinically assessed low rigidity were observed, suggesting that activated rigidity may be independent of resting rigidity and should be scored as independent variables. Moreover, we found that fall history was more common among people whose rigidity was increased with a secondary task, as measured by biomechanical outcomes. We conclude that different mechanisms contributing to resting and activated rigidity may play an important yet unexplored functional role in balance impairments. The pendulum test may contribute to a better understanding of fundamental mechanisms underlying motor symptoms in PD, evaluating the efficacy of treatments, and predicting the risk of falls.

Before birth, different organs retain hematopoiesis. The liver is involved in the 6th-8th week of gestation. The hepatic hematopoietic stem cell (HSC) niche begins when HSCs colonize the liver and make contact with sinusoidal endothelial cells. The aim of this study is to characterize the development of each hematopoietic cell lineage in 9 human liver specimens between 10 and 29 weeks of gestation with immunohistochemistry. Hematopoietic activity was coherent with gestational age. Erythropoiesis was the greatest fraction of fetal liver hematopoiesis: myeloid/erythroid ratio was inverted compared to the adult bone marrow. Myelopoiesis was compartmentalized in the periportal zone. Factor-VIII-positive cells were small, with a megakaryoblast-like morphology. Lymphoid precursors were absent. A small quantity of T and B lymphocytes was found. CD34-reactive hematopoietic stem and progenitor cells were found in a minority of cells. The understanding of the hematopoietic process during gestation could in the future contribute to better understand child and adult hematologic conditions.

Infections often complicate the course of hematological diseases and may represent a diagnostic challenge. In particular, visceral leishmaniasis diagnosis may be missed in lymphoma patients, as lymphoma-related immunosuppression can lead to a misleadingly negative Leishmania serology and to atypical clinical manifestations, including the lack of fever, considered a common symptom in leishmaniasis. Herein, we report a case of visceral leishmaniasis in a patient with a long history of B-cell chronic lymphocytic leukemia presenting with increasing fatigue and diarrhea, in the absence of fever. Leishmania serology was negative. Bone marrow biopsy performed with the clinical suspicion of transformation to high-grade lymphoma disclosed intracytoplasmic inclusion bodies resembling Leishmania amastigotes within the cytoplasm of macrophages, and CD1a immunohistochemical expression helped to confirm the diagnosis of leishmaniasis. Liposomal amphotericin B was administered with complete symptom resolution. The correct identification of Leishmania is critical as visceral leishmaniasis represents a severe disease with an often fatal outcome, particularly in frail patients, unless promptly recognized and adequately treated. A review of the literature of visceral leishmaniasis cases occurring in B-cell chronic lymphocytic leukemia patients is performed.

Abstract Background Intravascular lymphoma is a rare type of non-Hodgkin lymphoma mostly of B-cell lineage. A few cases of intravascular lymphoma have been found to be of NK/T-cell origin, mainly affecting the skin and central nervous system. Case presentation A 54-year-old Caucasian man sought care because of a 2 weeks history of jaundice and intermittent fever, not responsive to antibiotics and antipyretics. Laboratory tests showed low blood oxygen concentration and pancytopenia. Serum microbiological tests were negative. Computerized tomography (CT) scan revealed hepatosplenomegaly and diffuse ground-glass opacities in both lungs without interlobular septal thickening. Despite oxygen therapy, the clinical conditions rapidly deteriorated leading to death 3 days after admission. Autopsy revealed a multiorgan involvement by an Epstein-Barr virus positive NK/T-cell lymphoma, strikingly growing within the blood vessel lumina, in absence of skin lesions. Conclusions The current case highlights the pathological features of this rare entity, the protean clinical presentation of which is often misleading, resulting in delayed diagnosis and treatment.

A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 inhibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multicentric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for which he is currently on antibiotic therapy.

Histoplasma capsulatum is a dimorphic fungus, endemic in the Americas, Africa (var. duboisii), India, and Southeast Asia. H. capsulatum infection is rarely diagnosed in Italy, while in Latin America, progressive disseminated histoplasmosis (PDH) is one of the most frequent AIDS-defining illnesses and causes of AIDS-related deaths. We report a case of PDH and new HIV infection diagnosis in a Cuban patient, who has been living in Italy for the past 10 years. Bone marrow aspirate and peripheral blood smear microscopy suggested H. capsulatum infection. The diagnosis was confirmed with the culture method identifying its thermal dimorphism. Liposomal amphotericin B was administered alone for 10 days and then for another 2 days, accompanied with voriconazole; the former was stopped for probable side effects (persistent fever and worsening thrombocytopenia), and voriconazole was continued to complete 4 weeks. PDH maintenance treatment consisted of itraconazole for one year. Antiretroviral therapy (ART) was started on the third week of antifungal treatment. At the 3-year follow-up, the patient is adherent on ART, the virus was suppressed, and she has an optimal immune recovery. This case highlights the need to suspect histoplasmosis in the differential diagnosis of opportunistic infections in immunocompromised persons, native to or who have traveled to endemic countries.

A 79-year-old woman presented with a long history of peripheral eosinophilia. Previous right hemicolectomy for colonic polyposis was reported. Laboratory tests were notable for mild macrocitic anaemia and eosinophilia. β2 microglobulin and serum tryptase levels were elevated. Serum immunofixation revealed IgA/kappa monoclonal protein. Bence-Jones protein was positive. Bone marrow (BM) biopsy revealed the coexistence of two neoplastic components. Cohesive clusters of bland-looking, spindle-shaped mast cells, representing 20% of marrow cellularity, were close to aggregates of mature plasma cells occupying 40% of marrow cellularity. Molecular analysis on marrow aspirate demonstrated KIT D816V mutation, TET2 mutation, monoallelic deletion of TP53/17p13 and trisomy of ATM/11q23. A bone density study revealed mild osteoporosis. Full skeletal X-rays and magnetic resonance imaging (MRI) of spine and hips showed multiple, small rarefaction areas and an old L1-L2 fracture, both ascribed to osteoporosis. The association of systemic mastocytosis (SM) and multiple myeloma (MM) is very uncommon. The coexistence of SM with MM placed our patient in the SM with associated clonal haematological non-mast-cell lineage disease (SM-AHN) subtype. Midostaurin therapy was started.

Sea level rise is one of the main risk factors for the preservation of cultural heritage sites located along the coasts of the Mediterranean basin. Coastal retreat, erosion, and storm surges are posing serious threats to archaeological and historical structures built along the coastal zones of this region. In order to assess the coastal changes by the end of 2100 under the expected sea level rise of about 1 m, we need a detailed determination of the current coastline position based on high resolution Digital Surface Models (DSM). This paper focuses on the use of very high-resolution Unmanned Aerial Vehicles (UAV) imagery for the generation of ultra-high-resolution mapping of the coastal archaeological area of Pyrgi, Italy, which is located near Rome. The processing of the UAV imagery resulted in the generation of a DSM and an orthophoto with an accuracy of 1.94 cm/pixel. The integration of topographic data with two sea level rise projections in the Intergovernmental Panel on Climate Change (IPCC) AR5 2.6 and 8.5 climatic scenarios for this area of the Mediterranean are used to map sea level rise scenarios for 2050 and 2100. The effects of the Vertical Land Motion (VLM) as estimated from two nearby continuous Global Navigation Satellite System (GNSS) stations located as close as possible to the coastline are included in the analysis. Relative sea level rise projections provide values at 0.30 ± 0.15 cm by 2050 and 0.56 ± 0.22 cm by 2100 for the IPCC AR5 8.5 scenarios and at 0.13 ± 0.05 cm by 2050 and 0.17 ± 0.22 cm by 2100, for the IPCC Fifth Assessment Report (AR5) 2.6 scenario. These values of rise correspond to a potential beach loss between 12.6% and 23.5% in 2100 for Representative Concentration Pathway (RCP) 2.6 and 8.5 scenarios, respectively, while, during the highest tides, the beach will be provisionally reduced by up to 46.4%. In higher sea level positions and storm surge conditions, the expected maximum wave run up for return time of 1 and 100 years is at 3.37 m and 5.76 m, respectively, which is capable to exceed the local dune system. With these sea level rise scenarios, Pyrgi with its nearby Etruscan temples and the medieval castle of Santa Severa will be exposed to high risk of marine flooding, especially during storm surges. Our scenarios show that suitable adaptation and protection strategies are required.

Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analysed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years) and 33 typically developing (TD) children (1-12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behaviour.

Spastic gait is a key feature in patients with hereditary spastic paraparesis, but the gait characterization and the relationship between the gait impairment and clinical characteristics have not been investigated.To describe the gait patterns in hereditary spastic paraparesis and to identify subgroups of patients according to specific kinematic features of walking.We evaluated fifty patients by computerized gait analysis and compared them to healthy participants. We computed time-distance parameters of walking and the range of angular motion at hip, knee, and ankle joints, and at the trunk and pelvis. Lower limb joint moments and muscle co-activation values were also evaluated.We identified three distinct subgroups of patients based on the range of motion values. Subgroup one was characterized by reduced hip, knee, and ankle joint range of motion. These patients were the most severely affected from a clinical standpoint, had the highest spasticity, and walked at the slowest speed. Subgroup three was characterized by an increased hip joint range of motion, but knee and ankle joint range of motion values close to control values. These patients were the most mildly affected and had the highest walking speed. Finally, subgroup two showed reduced knee and ankle joint range of motion, and hip range of motion values close to control values. Disease severity and gait speed in subgroup two were between those of subgroups one and three.We identified three distinctive gait patterns in patients with hereditary spastic paraparesis that correlated robustly with clinical data. Distinguishing specific features in the gait patterns of these patients may help tailor pharmacological and rehabilitative treatments and may help evaluate therapeutic effects over time.

Water discharge assessment in open channel flow is one of the most crucial issues for hydraulic engineers in the fields of water resource management, river dynamics, ecohydraulics, irrigation, and hydraulic structure design, among others. Recent studies state that the entropy velocity law allows expeditive methodology for discharge estimation and rating curve development due to the simple mathematical formulation and implementation. Many works have been developed based on the one-dimensional (1-D) formulation of the entropy velocity profile, supporting measurements in the lab and the field for rating curve assessment, but in recent years, the two-dimensional (2-D) formulation was proposed and applied in studies of regular ditch flow, showing good performance. The present work deals with a comparison between the 1-D and 2-D approaches in order to give a general framework of threats and opportunities related to the robust operational application of such laws. The analysis was carried out on a laboratory ditch with regular roughness, under controlled boundary conditions, and in different stages, generating an exhaustive dashboard for better appraisal of the approaches.

Background: Piperazines, synthetic compounds known for their stimulant and hallucinogenic effects, have gained prominence among novel psychoactive substances (NPS) and are frequently associated with adverse psychiatric outcomes, including psychosis. Methods: A systematic review of the literature available up to 23 May 2024 was conducted, using the PubMed, Scopus, and Web of Science databases, in addition to the related gray literature, utilizing the following search strategy: “piperazines” AND (“psychosis” OR “hallucination” OR “delusion” OR “schizophrenia” OR “delusional” OR “schizoaffective”) NOT review NOT animal. Data collection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research methods were registered with PROSPERO (CRD42024549204). Results: Out of a total of 4547 articles identified, 4 met the inclusion criteria. We observed an important relationship between piperazine abuse and the onset of acute psychotic episodes, marked by symptoms such as paranoia, auditory, and visual hallucinations. Conclusion: The complex polyreceptor action mechanism of piperazines may explain these psychopathological effects, similar to those observed with other NPS. Although studies confirm a link between piperazine use and psychosis, data on long-term outcomes are limited. Recovery is common following cessation and treatment. Further research into the effects of piperazine abuse and the development of specific treatment protocols for substance-induced psychosis is necessary.

BackgroundMethylphenidate (MPH), a central nervous system stimulant primarily prescribed for attention-deficit/hyperactivity disorder (ADHD), has seen increasing rates of misuse and abuse, particularly in patients with dual diagnosis (co-occurring psychiatric disorders and substance use disorders/SUDs). The heightened risk of dependence and adverse effects in these vulnerable populations warrants a systematic review to assess the prevalence and pattern of abuse/misuse of MPH among patients within this population and to understand potential risk factors, patterns of misuse, and outcomes, including the impact on psychiatric symptoms and overall mental health, the effects on SUD (e.g., exacerbation or mitigation of symptoms), and the incidence of adverse events and complications (e.g., cardiovascular issues, psychological effects).MethodologyA systematic review was conducted in August-September 2024 using both PubMed and Scopus databases. The following search strategy was used: TITLE-ABS-KEY (methylphenidate OR Ritalin OR Concerta) AND TITLE-ABS-KEY (abuse OR misuse OR dependency OR addiction) AND TITLE-ABS-KEY (dual diagnosis OR comorbid psychiatric disorder OR psychiatric disorder AND substance use disorder). The systematic review was structured in accordance with the PRISMA guidelines and identified studies were assessed by title/abstract and full text screening against eligibility criteria.ResultsA total of 12 studies were selected for analysis after screening for relevance, quality, and adherence to inclusion criteria. Findings indicated that individuals with psychiatric disorders, particularly conduct disorder (N=593/1551 individuals), mood disorder (N=90/1551 individuals), anxiety disorder (N=66/1551 individuals), personality disorder (N=44/1551 individuals) and major depression disorder (N=40/1551 individuals), were more likely to misuse MPH. Co-occurring SUD, especially involving Alcohol Use Disorder (N=475/1551 individuals), Cannabis Use Disorder (N=371/1551 individuals), Nicotine Use Disorder (N=343/1551 individuals), Cocaine Use Disorder (N=68/1551 individuals), significantly elevated the risk. Misuse often involved higher doses than prescribed (N=84/1551 individuals) or using non-oral routes of administration (N=20/1551 individuals; e.g., snorting). Adverse outcomes included heightened risk of gastrointestinal events (N=201/1551 individuals), cardiovascular events (N=108/1551 individuals), psychosis (N=69/1551 individuals), and exacerbation of psychiatric symptoms (N=1082/1551 individuals).ConclusionMPH misuse and abuse are significant concerns in patients with psychiatric disorders and SUD. Risk factors include impulsivity, history of substance abuse, and access to prescription stimulants. Integrated therapeutic approaches and stricter prescription monitoring are recommended to mitigate misuse risks.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024576724.